|Ahead of print
Survival outcomes of pneumonectomy with left atrial resection for non-small cell lung cancer
Ali Celik, Muhammet Sayan, Nur D Ozkan, Aynur Bas, Ismail C Kurul, Abdullah I Tastepe
Department of Thoracic Surgery, Gazi University School of Medicine, Besevler, Ankara, Turkey
|Date of Submission||07-Aug-2019|
|Date of Decision||21-May-2020|
|Date of Acceptance||08-Jun-2020|
|Date of Web Publication||27-Jan-2021|
Department of Thoracic Surgery, Gazi University School of Medicine, Besevler, Ankara
Source of Support: None, Conflict of Interest: None
Background: Lung cancer invading left atrium is accepted as T4 tumor and surgical treatment in this situation is controversial. The aim of our study was to determine the prognostic factors of patients with surgically treated non-small cell lung cancer (NSCLC) invading left atrium.
Methods: After the approval of local ethics committee, the study was conducted in Gazi University, Department of Thoracic Surgery (Ankara-Turkey). The records of the patients were obtained from the encrypted hospital management software. Sequential codes were given to the data of patients and it was transferred to the statistics program without their names and ID numbers. The data of patients were collected as follows: those who had extended pneumonectomy from the surgery reports were found, then their pathology reports were examined, and those who had atrial muscle tissue were included in the study. Selected cases included as follows: patients who were medically suitable for surgery, patients who could tolerate surgery in cardiology evaluation, patients who had adequate lung capacity for pneumonectomy. Data of patients were analyzed according to age, gender, lymph node invasion, complete resection, and operative mortality.
Results: A total of 18 patients were included in the study. There were 16 (88.8%) men and 2 (12.2%) women. The mean age was 60.8 (range: 44 -76; Standard deviation: ± 1.8) years. Cardiopulmonary bypass was used in only one patient. The 30-day mortality was 5.5%. 1, 3, and 5-years overall survivals were 77%, 18.6%, and 9.3%, respectively. Mediastinal lymph node metastasis in N1 and N2 stations was detected 10 and 2, respectively. There was statistically significant correlation between recurrence and lymph node invasion status including N1 and N2 station (P = 0.04).
Conclusion: Although surgery is controversial in patients with NSCLC invading left atrium, it can be performed in selected cases. Morbidity and mortality rates were acceptable.
Keywords: Atrial resection, atrium invasion, lung cancer, pneumonectomyKey Message Although surgery is controversial in patients with non-small cell lung cancer invading left atrium, it can be performed in selected cases. Morbidity and mortality rates of that procedure are acceptable.
|How to cite this URL:|
Celik A, Sayan M, Ozkan ND, Bas A, Kurul IC, Tastepe AI. Survival outcomes of pneumonectomy with left atrial resection for non-small cell lung cancer. Indian J Cancer [Epub ahead of print] [cited 2021 Oct 24]. Available from: https://www.indianjcancer.com/preprintarticle.asp?id=308052
| » Introduction|| |
Lung cancer is the leading cause of cancer-related deaths worldwide. According to the current eighth TNM staging system proposed and applied by International Association for the Study of Lung Cancer (IASCL), the atrium wall invasion is considered as T4 tumor. It has been reported in the literature, with the surgical treatment, increase in survival can be achieved in the selected patients with non-small cell lung cancer (NSCLC) invading left atrium., According to the literature, treating NSCLC invading the left atrium by non-surgical methods has low survival outcomes, but complete resection and adjuvant chemo-radiotherapy result in better outcomes. Lymph node invasion and complete resection were found to be important prognostic factors in mentioned studies. However, there are also studies suggesting that the complete resection is not a prognostic factor in the literature.,, Therefore, discussions on this issue still continue. The aim of our study was determining the prognostic factors of patients with surgically treated NSCLC invading left atrium.
| » Subjects and Methods|| |
After the approval of the local ethics committee (Gazi University Ethics Committe, document number: 2018-209), the patients who underwent pneumonectomy with the diagnosis of NSCLC with atrial invasion between January 2001 and December 2017 were retrospectively analyzed. Patients who underwent intrapericardial pneumonectomy but those whose histopathologic examination could not demonstrate the atrial muscle tissue were not included in the study. The medical records of patients were analyzed according to age, gender, stage of tumor, postoperative complications, operative mortality, and survival.
Routine blood tests, pulmonary function tests, diffusing capacity of the lungs for carbon monoxide (DLCO), maximum oxygen uptake capacity (VO2max), ventilation/perfusion scan, electrocardiography, positron emission tomography-computed tomography (PET-CT) and echocardiography were done. If necessary, coronary angiography was performed. To determine the invasion of atrium, thorax computed tomograpghy (CT) angiography was performed [Figure 1]a. In some patients, cardiac magnetic resonance imaging (MRI) or trans-esophageal echocardiography (TEE) or both were performed to evaluate the preoperative resectability.
|Figure 1: (a) The Thorax CT.angiography shows lung cancer invading the left atrium. (b) The macroscopic view of resected specimen|
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In the patients with mediastinal lymph node, increased uptake of 18F-Fluorodeoxyglucose (18F-FDG) on PET/CT or patients with lymph node greater than 1 cm on thorax CT, mediastinal lymph node biopsy was performed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). When mediastinal lymph node invasion was not detected in thorax CT, PET-CT, and mediastinoscopy, surgery was planned, otherwise patients were referred to curative chemo-radiotherapy.
Patients were intubated with double-lumen tube. A posterolateral thoracotomy was performed.
The pericardium was incised in front of the phrenic nerve, protecting it. Incision was extended to pulmonary artery and it was encircled intrapericardially. The pericardial incision was then extended to the level of the inferior pulmonary vein and bronchus. At this stage, the left atrium invasion was re-evaluated. Left atrium was clamped beyond the proximal level of the pulmonary vein cuff by Satinsky clamp and hemodynamic status of patients was evaluated. When hemodynamic instability was not observed, pulmonary artery and bronchus were divided, respectively. 3-0 polypropylene suture with teflon pledget was placed at both ends of the Satinsky clamp. The pneumonectomy procedure was completed by making an atrium incision throughout the Satinsky clamp and the lung was removed. Atrium muscle was marked with silk suture on the specimen to guide the pathologist [Figure 1]b. The atrium stump was sutured by continuous suturing technique with polyprolene with teflon pledget. Then the clamp was opened to check the bleeding.
Similar to left-sided, the pericardium was incised in front of the phrenic nerve, protecting it. The right main pulmonary artery was encircled intrapericardially and suspended by nylon tape. The pericardial incision was then extended to the level of the inferior pulmonary vein and bronchus. Left atrium was clamped beyond the proximal level of the pulmonary vein cuff by Satinsky clamp, and hemodynamic status of patients was evaluated. In situations where there was not enough distance for placing the Satinsky clamp to left atrium, the interatrial groove was gently dissected by the Sondergaard technique to gain distance. After the atrial clamping, if the patient's hemodynamics was stable and there was no severe cardiac arrhythmia, first pulmonary artery and then bronchus were divided. Pulmonary resection and atrium saturation were completed, similar to the left-side.
After removal of the lung, appropriate mediastinal lymph node dissection was performed. Lymph node dissection routinely included excision of the subcarinal, hilar, upper and lower paratracheal lymph nodes with the fat pad for right-sided resection and subcarinal, paratracheal, paraaortic, aortico-pulmonary window stations for left-side resection. In addition, if detected, paraesophageal and pulmonary ligament lymph nodes were also dissected. Lymph nodes (hilar, intrapulmonar stations) on the pneumonectomy material were dissected by the pathologist and added to the pathology report. The cardiopulmonary bypass was required in a patient who developed hemodynamic instability and hypotension after left atrial clamping. All patients were extubated after the surgery—except this patient with the cardiopulmonary bypass—and then all of them were interned in intensive care unit. Postoperative pain control was achieved by epidural catheter or patient-controlled analgesia (PCA). Patients who completed intensive care follow-up were admitted to the sickroom. The death occurred within 30 days after the surgery was determined as operative mortality.
All analyses were performed using IBM-SPSS 20.2 for windows version. The overall survival (OS) was defined as the length of time from surgery to death or the final follow-up. Overall survival was calculated with Kaplan–Meier method including 95% confidence intervals. Survival differences between groups were analyzed using the Log-Rank and Cox-Regression tests. Two-sided P values were calculated and P value less than 0.05 were considered to be statistically significant.
| » Results|| |
Median follow-up of our study was 18.0 months. The patient's characteristics are given in [Table 1]. A total of 18 patients were included in the study. Sixteen (88.1 %) patients were men, 2 (11.1 %) were women. Mean age was 60.8 (range: 44–76, standard deviation (SD): ± 1.8) years. Eleven (61%) patients had right-sided and 7 (39%) patients had left-sided tumor. The mean tumor diameter was 4.9 cm. Histopathologically, squamous cell carcinoma (SCC) was detected in 13 (72.2%) patients, adenocarcinoma in 4 (22.2%) patients and combined large and small cell neuroendocrine carcinoma in 1 (5.6%) patient. Complete (R0) resection was achieved in 15 (83%) patients. Microscopic residual tumor (R1 resection) was detected in 2 patients at the atrial margin and 1 patient at the bronchial margin. One patient died of pneumonia on the 15th postoperative day. So the operative mortality rate was 5.5%. Two patients did not receive adjuvant therapy because of hemodynamic instability and laboratory parameters. The median survival was 24 (range=16.0–42.5) 1-, 3-, and 5-year OS were 77%, 18.6%, and 9.3%, respectively [Figure 2]. The number of patients alive after 24, 36 and 60 months were 10, 4 and 1, respectively. One patient lived 68 months and he is still alive. Five patients who were operated on different dates are still alive and their mean survival was 38.6 months. There was no statistically significant difference between survival and lymph node metastasis and R0 resection (P > 0.05). Local recurrence or distant metastasis was detected in 7 of 18 (38.8 %) patients. Median disease-free survival (DFS) was 21 (range=11-30.9) months. The presence of lymph node invasion (N1-N2) was found to be associated with recurrence [[Figure 3], P = 0.04].
|Figure 2: Overall survival curve of patients obtained by Kaplan-Meier method is seenIndian|
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|Figure 3: There was statistically significant correlation between mediastinal lymph node invasion and disease-free survival (P = 0.04) (LNI (+): lymph node invasion positive group, LNI (-):lymph node invasion negative group)|
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Patients with NSCLC who have locally advanced invasion are often not suitable for surgery, but surgery is recommended by some authors even in patients with T4N1M0 tumors which is suitable for complete resection. Left atrial invasion in lung cancer may occur as direct invasion or tumor embolism. Studies have indicated that if complete resection is achieved in these patients, an increase in survival is achieved. In the literature, particular attention is paid to the distinction between atrial resection and intra-pericardial pulmonary vein excision. It should be stated as atrial muscle tissue in the pathology report to define the operation as an atrial resection., We have included patients who fulfilled this condition in this study. Although CT angiography provides important information for atrial invasion in lung cancer, cardiac MRI and TEE may be needed for decision of resectability. Because right pulmonary veins are shorter, atrium invasion is more common in right-sided lung cancers. This condition can be compensated by interatrial groove dissection in right-sided tumors. It has been reported that invasion of adjacent mediastinal organs such as esophagus and aorta is more common in the lleft-sided tumors. In accordance with the literature, in our study, 11 patients had right-sided and 7 patients had left-sided tumor. The technique of dissecting the interatrial groove originally defined by Sondergaard and Walti for the closure of the patent foramen ovale is adapted to atrial-invasive lung cancer to increase amount of atrial cuff to be resected in right-sided tumors. Filaire et al. claimed that 4 cm atrium can be resected from the pulmonary vein border with the dissection of the interatrial groove. In our study, interatrial groove dissection was performed in all of the right resections to provide R0 resection and to facilitate atrial resection. In our patients, R1 resections at the atrial border were detected in left-sided tumors. It has been reported that in some articles, the risk of hematological metastasis, postoperative bleeding and lung dysfunction increases with bypass-guided lung cancer surgery, whereas some authors suggested that it has no adverse effects on long-term survival.,,, In our study, cardio-pulmonary by pass (CPB) was used in 1 patient and no statistically significant correlation was found between use of CPB and survival. It has been reported in the literature that the morbidity of atrium resection is high and that its operative mortality (within 1 month postoperatively) is between 0 and 18% in different series., Ksumoto et al. reported that 14 patients had postoperative major complications, 1 patient required re-exploration due to bleeding, 1 patient had broncho-arterial fistula-related death, and operative mortality was 7.1%. Tsuikoka et al. reported a prolonged air leak complication in 12 patients (16.6%) and no operative mortality. Spaggiari et al. reported that 2 patients (13.3%) had atrial arrhythmia that was cured with medical treatment and did not detect operative mortality. Galvaing et al. reported that bronchopleural fistula was developed in 1 patient, respiratory failure because of contralateral pulmonary complication occurred in 2 patients and operative mortality was 10.5%. In our study, mortality was observed in 1 patient because of contralateral pneumonia and sepsis on the 15th postoperative day. Thus, our operative mortality was detected as 5.5%. In our series, arrhythmia (atrial fibrillation or atrial tachycardia) developed in 5 patients, empyema without fistula in 2 patients, and minor bronchopleural fistula treated tube thoracostomy and antibiotherapy in 1 patient.
Some prognostic factors have been identified in various series including left atrial resection for NSCLC which is summarized in [Table 2]. No survival difference between N1 and N0 patient groups in Ratto's, Galvaing's and Tsuioka's series whereas in the N2 group, survival was significantly worse.,, Kuehnlet et al. emphasized that R0 resection and tumor grade have significant prognostic importance in 35 cases. Ratto et al. determined that survival is not affected by tumor histologic type, complete resection. In our study, lymph node metastasis was detected in 10 patients in N1 stations and in 2 patients in N2 stations. Median survival of groups with positive (N1 and N2 station) and negative lymph node metastasis was 22 months (13.4–30.6) and 26 months (8.4–42.4), respectively and that difference was not statistically significant (P = 0.1). Microscopic residual tumor was detected at surgical margin of atrium in 2 patients and at main bronchus in 1 patient. In our study, there were no significant differences in OS and DFS between complete and incomplete resections. The studies supporting our results in literature were available.
|Table 2: The outcomes of various studies related pneumonectomy with atrial resection for non.small cell lung cancer in the literature|
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The 5-year OS was reported as 3–17% in patients with advanced invasive T4 lung cancer treated with non-operative methods. Survival outcomes in patients underwent lung resection with left atrium resection include a very wide range that 5-year OS was 0–43%.,,, Results of 5-year survival of various related studies including with or without induction therapy were given in Table 2. In our study, operative mortality, median survival and 1-3-5 year OS were compatible with the literature. One patient in our study has been living for more than 60 months without tumor recurrence or metastasis and he is still alive. There was no statistically significant difference between survival and lymph node metastasis and R0 resection (P > 0.05). There was no recurrence in 6 patients who had no mediastinal lymph node metastasis in pathological examination. The correlation between lymph node metastasis and DFS was statistically significant (P = 0.04). Recurrence was not detected in 2 of 3 patients who received adjuvant chemo-radiotherapy due to R1 resection. Furthermore, there was no statistically significant correlation between complete resection and DFS (P > 0.05). In summary it can be said that, the results of surgery performed for lung cancers with atrium invasion were acceptable in terms of DFS and OS.
The limitations of our study were as follows: it was a retrospective and single-centered study, and it included a few cases. Moreover, the distribution of patients was not homogeneous in groups that received and did not receive neoadjuvant therapy; thus, we could not make effective comparative statistical analysis between these groups. Our results need to be supported by multicentre and prospective studies if possible.
| » Conclusions|| |
Surgical treatment for locally advanced NSCLC invading left atrium is controversial due to its unsatisfactory survival time and morbidity. However it can be performed in well selected cases. Patients who can tolerate surgery in terms of cardiac status and lung capacity for pneumonectomy may be candidate for surgery.
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Conflicts of interest
There are no conflicts of interest.
| » References|| |
Galvaing G, Chadeyras JB, Merle P, Tardy MM, Naamee A, Bailly P, et al. Extended resection of non-small cell lung cancer invading the left atrium, is it worth the risk? Chin Clin Oncol 2015;4:43.
Langer NB, Mercier O, Fabre D, Lawton J, Mussot S, Dartevelle P, et al. Outcomes after resection o T4 non-small cell lung cancer using cardiopulmonary bypass. Ann Thorac Surg 2016 ;102:902-10.
Wu L, Xu Z, Zhao X, Li J, Zhong L, Li J, et al. Surgical treatment of lung cancer invading the left atrium or base of the pulmonary vein. World J Surg 2009 ;33:492-6.
Bernard A, Bouchot O, Hagry O, Favre JP. Risk analysis and long-term survival in patients undergoing resection of T4 lung cancer. Eur J Cardiothorac Surg 2001;20:344-9.
Ratto GB, Costa R, Vassallo G, Alloisio A, Maineri P, Biruzzi P. Twelve-year experience with left atrial resection in the treatment of non-small cell lung cancer. Ann Thorac Surg 2004;78:234-7.
Doddoli C, Rollet G, Thomas P, Ghez O, Serée Y, Giudicelli R, et al. Is lung cancer surgery justified in patients with direct mediastinal invasion? Eur J Cardiothorac Surg 2001;20:339-43.
Chambers A, Routledge T, Billè A, Scarci M. Does surgery have a role in T4N0 and T4N1 lung cancer? Interact Cardiovasc Thorac Surg 2010;11:473-9.
Tsukioka T, Takahama M, Nakajima R, Kimura M, Inoue H, Yamamoto R. Surgical outcome of patients with lung cancer involving the left atrium. Int J Clin Oncol 2016;21:1046-50.
Spaggiari L, D' Aiuto M, Veronesi G, Pelosi G, de Pas T, Catalono G, et al. Extended pneumonectomy with partial resection of the left atrium, without cardiopulmonary bypass, for lung cancer. Ann Thorac Surg 2005;79:234-40.
Pinto CA, Marcella S, August DA, Holland B, Kostis JB, Demisse K. Cardiopulmonary bypass has a modest association with cancer progression: A retrospective cohort study. BMC Cancer 2013;13:519.
Filaire M, Nohra O, Sakka L, Chadeyras JB, Da Costa V, Naamee A, et al. Anatomical bases of the surgical dissection of the interatrial septum: A morphological and histological study. Surg Radiol Anat 2008;30:369-73.
Muralidaran A, Detterbeck FC, Boffa DJ, Wang Z, Kim AW. Long-term survival after lung resection for non-small cell lung cancer with circulatory bypass: A systematic review. J Thorac Cardiovasc Surg 2011;142:1137-42.
Byrne JG, Leacche M, Agnihotri AK, Paul S, Bueno R, Mathisen DJ, et al. The use of cardiopulmonary bypass during resection of locally advanced thoracic malignancies: A 10-year two-center experience. Chest 2004;125:1581-6.
Kusumoto H, Shintani Y, Funaki S, Inoue M, Okumura M, Kuratani T, et al. Combined resection of great vessels or the heart for non-small lung cancer. Ann Thorac Cardiovasc Surg 2015;21:332-7.
Bobbio A, Carbognani P, Grapeggia M, Rusca M, Sartori F, Bobbio P, Rea F, et al. Surgical outcome of combined pulmonary and atrial resection for lung cancer. Thorac Cardiovasc Surg 2004;52:180-2.
Kuehnl A, Lindner M, Hornung HM, Winter H, Jauch KW, Hatz RA, et al. Atrial resection for lung cancer: Morbidity, mortality, and long-term follow-up. World J Surg 2010;34:2233-9.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]